Preclinical PET Imaging and Toxicity Study of a <sup>68</sup>Ga-Functionalized Polymeric Cardiac Blood Pool Agent
Cardiac blood pool imaging is currently performed almost exclusively with <sup>99m</sup>Tc-based compounds and SPECT/CT imaging. Using a generator-based PET radioisotope has a few advantages, including not needing nuclear reactors to produce it, obtaining better resolution in humans, and...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/3/767 |
| _version_ | 1797609601337655296 |
|---|---|
| author | Katayoun Saatchi François Bénard Navjit Hundal Joshua Grimes Sergey Shcherbinin Maral Pourghiasian Donald E. Brooks Anna Celler Urs O. Häfeli |
| author_facet | Katayoun Saatchi François Bénard Navjit Hundal Joshua Grimes Sergey Shcherbinin Maral Pourghiasian Donald E. Brooks Anna Celler Urs O. Häfeli |
| author_sort | Katayoun Saatchi |
| collection | DOAJ |
| description | Cardiac blood pool imaging is currently performed almost exclusively with <sup>99m</sup>Tc-based compounds and SPECT/CT imaging. Using a generator-based PET radioisotope has a few advantages, including not needing nuclear reactors to produce it, obtaining better resolution in humans, and potentially reducing the radiation dose to the patient. When the shortlived radioisotope <sup>68</sup>Ga is used, it can be applied repeatedly on the same day—for example, for the detection of bleeding. Our objective was to prepare and evaluate a long-circulating polymer functionalized with gallium for its biodistribution, toxicity, and dosimetric properties. A 500 kDa hyperbranched polyglycerol was conjugated to the chelator NOTA and radiolabeled rapidly at room temperature with <sup>68</sup>Ga. It was then injected intravenously into a rat, and gated imaging allowed us to easily observe wall motion and cardiac contractility, confirming the suitability of this radiopharmaceutical for cardiac blood pool imaging. Internal radiation dose calculations showed that the radiation doses that patients would receive from the PET agent would be 2.5× lower than those from the <sup>99m</sup>Tc agent. A complete 14-day toxicology study in rats concluded that there were no gross pathology findings, changes in body or organ weights, or histopathological events. This radioactive-metal-functionalized polymer might be a suitable non-toxic agent to advance for clinical application. |
| first_indexed | 2024-03-11T06:02:43Z |
| format | Article |
| id | doaj.art-e172bac4bc4d433fb094082fc756a4be |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:02:43Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e172bac4bc4d433fb094082fc756a4be2023-11-17T13:14:06ZengMDPI AGPharmaceutics1999-49232023-02-0115376710.3390/pharmaceutics15030767Preclinical PET Imaging and Toxicity Study of a <sup>68</sup>Ga-Functionalized Polymeric Cardiac Blood Pool AgentKatayoun Saatchi0François Bénard1Navjit Hundal2Joshua Grimes3Sergey Shcherbinin4Maral Pourghiasian5Donald E. Brooks6Anna Celler7Urs O. Häfeli8Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Radiology, University of British Columbia, Vancouver, BC V5Z 1M9, CanadaBC Cancer, Vancouver, BC V5Z 4E6, CanadaDepartment of Radiology, University of British Columbia, Vancouver, BC V5Z 1M9, CanadaDepartment of Radiology, University of British Columbia, Vancouver, BC V5Z 1M9, CanadaBC Cancer, Vancouver, BC V5Z 4E6, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Radiology, University of British Columbia, Vancouver, BC V5Z 1M9, CanadaFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaCardiac blood pool imaging is currently performed almost exclusively with <sup>99m</sup>Tc-based compounds and SPECT/CT imaging. Using a generator-based PET radioisotope has a few advantages, including not needing nuclear reactors to produce it, obtaining better resolution in humans, and potentially reducing the radiation dose to the patient. When the shortlived radioisotope <sup>68</sup>Ga is used, it can be applied repeatedly on the same day—for example, for the detection of bleeding. Our objective was to prepare and evaluate a long-circulating polymer functionalized with gallium for its biodistribution, toxicity, and dosimetric properties. A 500 kDa hyperbranched polyglycerol was conjugated to the chelator NOTA and radiolabeled rapidly at room temperature with <sup>68</sup>Ga. It was then injected intravenously into a rat, and gated imaging allowed us to easily observe wall motion and cardiac contractility, confirming the suitability of this radiopharmaceutical for cardiac blood pool imaging. Internal radiation dose calculations showed that the radiation doses that patients would receive from the PET agent would be 2.5× lower than those from the <sup>99m</sup>Tc agent. A complete 14-day toxicology study in rats concluded that there were no gross pathology findings, changes in body or organ weights, or histopathological events. This radioactive-metal-functionalized polymer might be a suitable non-toxic agent to advance for clinical application.https://www.mdpi.com/1999-4923/15/3/767Ga-68hyperbranched polyglycerolnon-toxic polymermacromoleculeblood pool imaging agentPET radiopharmaceutical |
| spellingShingle | Katayoun Saatchi François Bénard Navjit Hundal Joshua Grimes Sergey Shcherbinin Maral Pourghiasian Donald E. Brooks Anna Celler Urs O. Häfeli Preclinical PET Imaging and Toxicity Study of a <sup>68</sup>Ga-Functionalized Polymeric Cardiac Blood Pool Agent Pharmaceutics Ga-68 hyperbranched polyglycerol non-toxic polymer macromolecule blood pool imaging agent PET radiopharmaceutical |
| title | Preclinical PET Imaging and Toxicity Study of a <sup>68</sup>Ga-Functionalized Polymeric Cardiac Blood Pool Agent |
| title_full | Preclinical PET Imaging and Toxicity Study of a <sup>68</sup>Ga-Functionalized Polymeric Cardiac Blood Pool Agent |
| title_fullStr | Preclinical PET Imaging and Toxicity Study of a <sup>68</sup>Ga-Functionalized Polymeric Cardiac Blood Pool Agent |
| title_full_unstemmed | Preclinical PET Imaging and Toxicity Study of a <sup>68</sup>Ga-Functionalized Polymeric Cardiac Blood Pool Agent |
| title_short | Preclinical PET Imaging and Toxicity Study of a <sup>68</sup>Ga-Functionalized Polymeric Cardiac Blood Pool Agent |
| title_sort | preclinical pet imaging and toxicity study of a sup 68 sup ga functionalized polymeric cardiac blood pool agent |
| topic | Ga-68 hyperbranched polyglycerol non-toxic polymer macromolecule blood pool imaging agent PET radiopharmaceutical |
| url | https://www.mdpi.com/1999-4923/15/3/767 |
| work_keys_str_mv | AT katayounsaatchi preclinicalpetimagingandtoxicitystudyofasup68supgafunctionalizedpolymericcardiacbloodpoolagent AT francoisbenard preclinicalpetimagingandtoxicitystudyofasup68supgafunctionalizedpolymericcardiacbloodpoolagent AT navjithundal preclinicalpetimagingandtoxicitystudyofasup68supgafunctionalizedpolymericcardiacbloodpoolagent AT joshuagrimes preclinicalpetimagingandtoxicitystudyofasup68supgafunctionalizedpolymericcardiacbloodpoolagent AT sergeyshcherbinin preclinicalpetimagingandtoxicitystudyofasup68supgafunctionalizedpolymericcardiacbloodpoolagent AT maralpourghiasian preclinicalpetimagingandtoxicitystudyofasup68supgafunctionalizedpolymericcardiacbloodpoolagent AT donaldebrooks preclinicalpetimagingandtoxicitystudyofasup68supgafunctionalizedpolymericcardiacbloodpoolagent AT annaceller preclinicalpetimagingandtoxicitystudyofasup68supgafunctionalizedpolymericcardiacbloodpoolagent AT ursohafeli preclinicalpetimagingandtoxicitystudyofasup68supgafunctionalizedpolymericcardiacbloodpoolagent |